Bioinformatic analysis of SIRT7 sequence and structure

Sirtuins are highly conserved proteins that perform very important functions in different cellular processes. Notably, SIRT7 is the least studied human sirtuin, but it is known to be involved in a wide variety of processes in both health and disease. In this way, SIRT7 activity-regulating molecules could be beneficial for the treatment of relevant diseases such as cardiovascular and bone diseases, where SIRT7 levels are reduced, or obesity and cancer, where they are increased. In this work, using bioinformatic methods, the sequence and structure of SIRT7 orthologs in a wide variety of organisms were analyzed. Thus, the catalytic domain was found to be quite conserved (83.23% identity) and key residues such as D118, Y119, R120, D170, H187, N189, C198, C225, C228, V273, G298, F239 and V237 were identified. Furthermore, a phylogenetic tree was constructed where SIRT7 orthologs from mammals, birds, reptiles, amphibians, fish, insects, and arachnids were found to cluster in different groups. Finally, predicted three-dimensional structures showed a classic structure of the central catalytic region of most sirtuins, while the flanking N- and C-terminal regions were unique to each phylogenetic group. All this helps to understand a little more how SIRT7 works and gives clues for the future design and development of small molecules that benefit human and animal health. Communicated by Ramaswamy H. Sarma